NEW YORK (Reuters Health) - The colon and ileum contain
dendritic cells with distinct roles in mucosal immunity, new
research finds.

The colon and the ileum should be regarded as separate
entities, each containing dendritic cells with distinct roles in
mucosal immunity and imprinting, the study authors reported
online February 9 in the British medical journal Gut.

"The regulatory properties of immune cells we observed in
the large bowel compared to the small bowel may be due to the
much greater bacterial load (commensal microflora) in the large
bowel," lead author Dr. Elizabeth R. Mann of the Johns Hopkins
University School of Medicine in Baltimore, Maryland, and
Imperial College London, United Kingdom, told Reuters Health in
an email.

"This study has direct relevance for inflammatory
intestinal diseases that affect specific compartments of the gut
- such as Crohn's disease - that can affect the large bowel
only, or the small bowel only, or both compartments
simultaneously," she wrote.

"Clinicians need to be cautious when trying to manipulate
intestinal microbiota, such as with fecal transplantation, as a
part of the clinical treatment of (gastrointestinal) GI diseases
or other relevant disorders. Rapid or dramatic alteration of the
gut luminal environment (microbiota), although increasingly
popular for treating some GI diseases, such as Clostridium
difficile infections and inflammatory bowel disease, may lead to
unwanted or unpredicted consequences due to the potential
inability or lower efficiency of our gut to readapt the altered
bacterial loads from the long-established evolutionary
adaptation," wrote coauthor Dr. Xuhang Li, also of the Johns
Hopkins University School of Medicine, in an email to Reuters
Health.

They found that a lower proportion of colonic dendritic
cells produced pro-inflammatory cytokines (tumor necrosis
factor-alpha and interleukin (IL)-1 beta) compared with their
ileal counterparts and exhibited an enhanced ability to generate
CD4+FoxP3+IL-10+ (regulatory) T cells. They also found enhanced
proportions of CD103+ Signal regulatory protein alpha (SIRP
alpha)  dendritic cells in the colon, with increased
proportions of CD103+Sirp alpha + dendritic cells in the ileum.

"The gut is unlike other tissues of the body in that it is
exposed to such a huge bombardment of antigens from ingested
food and commensal microflora (as well as any potentially
harmful pathogens). Therefore, immune responses in the gut are
unique," Dr. Mann wrote in an email.

Dr. Li added that clinicians and scientists have long
wondered why we don't often have major problems at the cellular
and molecular levels, despite our gigantic bacterial load.

"We have more microbes in our colon than all the cells that
compose our entire body," he wrote in an email.

"Now we know from our work and that of other scientists
that, through evolutionary adaptation, our colon has a lower
proportion of dendritic cells that produce pro-inflammatory
cytokines, while at the same time, colonic dendritic cells
exhibit an enhanced ability to generate immunosuppressive (also
called regulatory) T cells (T-regulatory cells). This enhanced
regulatory function can literally enable the colonic immune
system to ignore or 'pretend not to see' the large load of
bacteria present in the colon, thereby dampening the immune
response," Dr. Li explained.

"These findings also suggest that we may be able to
clinically manipulate the subpopulation of innate immune cells,
such as dendritic cells, to selectively increase the tolerogenic
(or regulatory, immunosuppressive) populations while we decrease
the inflammatory populations," he added.

Dr. Li advised that clinicians need to be careful when
manipulating the gut bacteria for therapeutic purposes, "because
our gut immune system has already adapted to what is present in
our gut. Any major change in the gut flora may upset the
homeostasis of the gut immunity and lead to unwanted
consequences."

This research was funded by St. Mark's Foundation, the
Biotechnology and Biological Sciences Research Council, and the
National Institutes of Health, with additional support from the
Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Centre
at Johns Hopkins Hospital. The authors stated that they had no
competing interests.